DESCRIPTION (From the applicant's abstract): Nervous system development and function are regulated by neuronal responses to an extensive repertoire of extracellular molecular stimuli. These stimuli influence neuronal cell survival, differentiation, axonal guidance, synapse formation, synaptic plasticity, and neurophysiological responses through an array of signal transduction mechanisms which are still poorly understood. My laboratory has uncovered a novel signaling module within neuronal cells that consists of a newly discovered protein kinase scaffold protein, a cascade of protein kinases, and a set of proteins previously thought to function extracellularly as growth factors. The experiments proposed within this application are expected to identify extracellular stimuli that signal through this novel kinase module and to determine the neurobiological consequences of this signaling pathway. In addition to the importance of defining the architecture and regulation of a new biochemical pathway, these studies are likely to significantly improve our understanding of mechanisms underlying neuronal development and function.